The overall objective of this research is to study the effects of viral interference on viral gene expression. In work already published, we have shown that clear plaque (C) mutants which arise in influenza virus populations can rapidly predominate in those hosts in which they can interfere with the replication of the parental virus (designated F for fuzzy plaque morphology). We wish to study the mechanism of this interference so that its role in the selection of mutants or recombinants can be evaluated. Specifically, we will characterize the virion RNAs of the two mutants and determine whether the RNA from the C variant inhibits transcription and/or replication of the F variant. In addition, we will investigate the mechanism by which these variants establish persistent infections in MDBK cells, and will characterize a virus-resistant MDBK cell line which we have obtained from persistently infected cell cultures. Information from these experiments should let us determine whether interferences of this type can be important in the epidemiology of influenza, whether it significantly affects the outcome of genetic analysis of these viruses, and whether it can be employed to obtain the virus strains of desired characteristics for vaccine use and for the investigation of virus properties such as virulence, transmissibility, and host range. The experiments should also provide information about the replication of the influenza viruses and about virus particle-induced interference.